Nucleic acids encoding single domain antibodies to chikungunya virus
Inventors
Liu, Jinny Lin • Anderson, George P. • Goldman, Ellen R.
Assignees
Government Of United States Of Americas Represented By Secretary Of Navy AS • US Department of Navy
Publication Number
US-11542320-B2
Publication Date
2023-01-03
Expiration Date
2039-07-17
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Abstract
Described herein are nucleic acids encoding single-domain antibodies that might serve as alternatives to conventional monoclonal antibodies for either the detection or treatment of Chikungunya Virus (CHIKV).
Core Innovation
The invention describes nucleic acids encoding single-domain antibodies (sdAb) that can serve as alternatives to conventional monoclonal antibodies for the detection or treatment of Chikungunya Virus (CHIKV). These sdAb are derived from camelid heavy-chain antibodies, possessing a single variable domain capable of antigen binding, offering high specificity and affinity. The isolated proteins include sequences identified as SEQ ID Nos. 1-14, developed through immunization of llamas with CHIKV virus-like particles and E1 protein.
The background recognizes the significant challenge posed by CHIKV as a mosquito-transmitted alphavirus causing polyarthritis and currently threatening spread to the United States due to the presence of its mosquito vector. Existing antibody-based therapeutics and diagnostics rely mostly on conventional IgGs, which are limited by their thermal instability, requirement for cold storage, and potential to exacerbate illness through Fc-mediated processes. There is no effective human vaccine or therapeutic currently available to protect against CHIKV infection, and there exists a need for robust methods for detection and effective therapeutics.
The invention addresses this need by developing sdAb that maintain antigen binding upon exposure to elevated temperatures, improving stability and suitability for point-of-care diagnostics without refrigeration. Furthermore, sdAb lack an Fc domain, potentially avoiding the adverse Fc-mediated effects seen with conventional IgG therapeutics for CHIKV. The sdAb exhibit high affinity and specificity to CHIKV E1 protein and virus-like particles and have been demonstrated to inhibit viral infection in vitro. Thus, these sdAb represent rugged, thermally stable detection reagents and therapeutic candidates against CHIKV.
Claims Coverage
The patent includes three independent claims focusing on nucleic acids encoding single-domain antibodies with specific protein sequences related to CHIKV binding.
Nucleic acid encoding single-domain antibodies comprising specific protein sequences
A nucleic acid encoding a single-domain antibody comprising any protein sequence selected from SEQ ID Nos. 1-14.
Nucleic acid encoding single-domain antibodies comprising selected protein sequences
A nucleic acid encoding a single-domain antibody comprising a protein sequence selected specifically from SEQ ID Nos. 1 and 13.
Nucleic acid encoding a single-domain antibody of a single protein sequence
A nucleic acid encoding a single-domain antibody comprising the protein sequence of SEQ ID No. 1.
These claims collectively cover nucleic acids encoding single-domain antibodies with particular protein sequences that bind CHIKV, emphasizing broad inclusion of 14 sequences and subsets thereof, indicating the invention's scope over nucleic acids encoding these key sdAb.
Stated Advantages
The single-domain antibodies exhibit robustness and thermal stability, capable of refolding after denaturation, enabling use in detection and therapeutic applications without cold storage requirements.
SdAb are smaller and lack the Fc domain, potentially avoiding adverse Fc-mediated immune effects associated with conventional antibodies used in CHIKV treatment.
SdAb offer higher specific activity per weight and faster tissue diffusion due to their small size.
These sdAb can be engineered with various fusion domains to enhance utility and are suitable for long-term field applications where refrigeration is not feasible.
Documented Applications
Use of single-domain antibodies in immunoassays for detecting Chikungunya virus infection, including enzyme-linked immunosorbent assays (ELISA) and MagPlex sandwich assays.
Use of single-domain antibodies as therapeutics to inhibit Chikungunya virus infection, demonstrated by the ability of certain sdAb to prevent infection of Vero cells.
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